A new way to artificially control muscles using light, with the potential to restore function to muscles paralysed by conditions such as motor neuron disease and spinal cord injury, has been developed by scientists at UCL and King’s College London.

The technique involves transplanting specially-designed motor neurons created from stem cells
into injured nerve branches. These motor neurons are designed to react to
pulses of blue light, allowing scientists to fine-tune muscle control by adjusting
the intensity, duration and frequency of the light pulses.

In
the study, published this week in Science,
the team demonstrated the method in mice in which the nerves that supply
muscles in the hind legs were injured. They showed that the transplanted stem
cell-derived motor neurons grew along the injured nerves to connect
successfully with the paralyzed muscles, which could then be controlled by
pulses of blue light.

“Following
the new procedure, we saw previously paralysed leg muscles start to function,” says
Professor Linda Greensmith of the MRC Centre for Neuromuscular Diseases at
UCL’s Institute of Neurology, who co-led the study. “This strategy has
significant advantages over existing techniques that use electricity to
stimulate nerves, which can be painful and often results in rapid muscle
fatigue. Moreover, if the existing motor neurons are lost due to injury or
disease, electrical stimulation of nerves is rendered useless as these too are
lost.”

Muscles
are normally controlled by motor neurons, specialized nerve cells within the
brain and spinal cord. These neurons relay signals from the brain to muscles to
bring about motor functions such as walking, standing and even breathing.
However, motor neurons can become damaged in motor neuron disease or following
spinal cord injuries, causing permanent loss of muscle function resulting in paralysis

This strategy has significant advantages over existing techniques that use electricity to stimulate nerves, which can be painful and often results in rapid muscle fatigue.

Professor Linda Greensmith (UCL Neurology)

“This
new technique represents a means to restore the function of specific muscles
following paralysing neurological injuries or disease,” explains Professor
Greensmith. “Within the next five years or so, we hope to undertake the steps
that are necessary to take this ground-breaking approach into human trials,
potentially to develop treatments for patients with motor neuron disease, many
of whom eventually lose the ability to breathe, as their diaphragm muscles gradually
become paralysed. We eventually hope to
use our method to create a sort of optical pacemaker for the diaphragm to keep
these patients breathing.”

The
light-responsive motor neurons that made the technique possible were created
from stem cells by Dr Ivo Lieberam of the MRC Centre for Developmental
Neurobiology, King’s College London.

“We
custom-tailored embryonic stem cells so that motor neurons derived from them
can function as part of the muscle pacemaker device.” says Dr Lieberam, who
co-led the study. “First, we equipped the cells with a molecular light sensor.
This enables us to control motor neurons with blue light flashes. We then built
a survival gene into them, which helps the stem-cell motor neurons to stay
alive when they are transplanted inside the injured nerve and allows them to grow
to connect to muscle.”